Prostate specific antigen (PSA) is a protease whose function is to break down the high molecular weight protein of the seminal coagulum into smaller polypeptides. This action results in the semen becoming more liquid. PSA is produced exclusively by epithelial prostatic cells, both benign and malignant. It is also found in the serum.¹ Serum PSA is currently the best method of detecting localised prostatic cancer and monitoring response to treatment but it lacks specificity as it is also increased in most patients with benign prostatic hypertrophy (BPH).²

Conditions which may have elevated PSA³

Causes include:

• Acute urinary retention
• Benign prostatic hyperplasia
• Old age
• Prostatitis
• Prostate carcinoma
• Transurethral resection of the prostate
• Urinary catheterisation

Normal range

The normal range is age-dependent and the Department of Health recommends the following 'cut-off' points:

Uses of the PSA test in prostate cancer diagnosis

The National Screening Debate

The issue of a national screening programme is a controversial one but there is currently little evidence to support such an initiative. A Health Technology Assessment concluded that a lack of specificity of the PSA test, a lack of knowledge of the epidemiology and natural history of the disease and a lack of information concerning the effectiveness and cost-effectiveness of the treatment of localised cancer, all argue against the institution of a national screening programme.⁴ Although the assessment was conducted in 1997, further work, most notably a Cochrane Review in 2006, has failed to resolve the issue and it is suggested that is will be several years before enough evidence is available to make definitive recommendations.⁵ Subsequent randomised trials have failed to shed any further light on the subject, suggesting that screening at best has a marginal effect on survival but there is a significant risk of overdiagnosis and over-treatment.⁶

Diagnosing Individual patients

The Department of Health realises that there are more than economic and clinical issues to take into account when applying the national policy to individual patients. They have therefore very wisely left it to individual patients to decide, after discussion with their doctor, whether to have a PSA test. A booklet has been produced by the Department of Health to assist this discussion.⁷

The patient needs to be apprised of the following points:

• Prostate cancer is but one of several causes of a raised PSA test.
• Because the test is nonspecific, all patients with a significantly raised PSA should have a prostate biopsy.
• One in five men with a normal PSA will have prostate cancer.
• Two out of three men with a raised PSA will not have cancer cells in their biopsy.
• There is no conclusive evidence that detection of early prostate cancer leads to longer survival.
• The test cannot distinguish between aggressive and slow-growing cancers and may detect tumours that would not otherwise become evident in the patient's lifetime.
• The test is of most value in patients who are 'high-risk' - i.e:
  • Aged above 70 years
  • Afro-Caribbeans
  • Patients with a positive family history

Monitoring the effects of treatment²

There is no conclusive evidence to determine the optimal treatment of localised prostate cancer and many urologists rely on rising PSA results to signal that a radical intervention (usually either chemotherapy or radiotherapy) is necessary. This is particularly appropriate for older patients with comorbidities, on the basis that they are likely to die of some other cause before a slow-growing prostate tumour has an effect on their lifespan. Such 'active monitoring' is also appropriate for any patient who wishes to avoid the side-effects of interventional management.⁸ New targeted treatments for castrate-resistant prostate cancer, however, have little effect on PSA levels and monitoring in these circumstances is more problematic.⁹

Practicalities of the PSA test²

At the time of the test, the patient should not have:

• An active urinary tract infection
• Ejaculated in the previous 48 hours
• Had a prostate biopsy in the previous six weeks
• Had a recent digital rectal examination (if possible, do the blood test before the examination; otherwise, wait for one week after)

Document references

1. Oesterling JE; Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol. 1991 May;145(5):907-23. [abstract]
2. Watson E, Jenkins L, Bukach C et al; The Prostate Cancer Risk Management Programme 2002.; Booklet for primary care teams issued by Department of Health
3. The PSA Test; Association for International Cancer Research 2010.
4. Selley S, Donovan J, Faulkner A et al; Health Technology Assessment 1997; Vol 1: number 2 1997.
5. Ilic D, O'Connor D, Green S, et al; Screening for prostate cancer. Cochrane Database Syst Rev. 2006 Jul 19;3:CD004720. [abstract]
6. Hoffman RM; Randomized trial results did not resolve controversies surrounding prostate Curr Opin Urol. 2010 Mar 10. [abstract]
7. NHS Direct; Prostate Cancer Risk Management: UK Information Pack; 2002
8. Improving Outcomes in Urological Cancers; NICE Guidance 2002; Links to pdf file
9. Payne H, Cornford P; Prostate-specific antigen: An evolving role in diagnosis, monitoring, and Urol Oncol. 2010 Jan 6. [abstract]

Internet and further reading

• Jain S, Bhojwani AG, Mellon JK; Improving the utility of prostate specific antigen (PSA) in the diagnosis of prostate cancer: the use of PSA derivatives and novel markers. Postgrad Med J. 2002 Nov;78(925):646-50. [abstract]

Acknowledgements